P&S Journal: Spring 1996, Vol.16, No.2Ethics in Medicine - Genetics: What to Know and When and Why

By Devera Pine

Dr. Claudio Stern

Every day, it seems, a report in the news media links yet another disease to a genetic defect. From depression to heart disease to cancer, it is increasingly clear that many diseases have genetic components. In fact, since the Human Genome Project began in 1987, scientists have uncovered some 100 genes or genetic markers involved in various diseases; other new findings are coming in almost daily.

"Our knowledge is growing at an exponential rate," says Dr. Paul B. Fisher, the Chernow Research Scientist in Pathology and Urology, professor of clinical pathology, and director of the neuro-oncology program at CPMC. "We will have a complete understanding of the human genome as time goes on."

That knowledge, however, comes with a price. With each new gene identified comes the ability to screen for a predisposition to genetic diseases-and, therefore, the power to discriminate in some form against those with the disease, or even those with merely the tendency to develop the disease. As a result, each new gene discovery brings a series of ethical issues, some with no right or wrong answer. Among them: Which genes should we screen for, both in adults and prenatally? What, if any, action should be taken based on the results of these screenings? And who has the right to this information?

Dr. Isidore Edelman

"There is this rushing train coming at us faster and faster," says Dr. Isidore S. Edelman, director of the Columbia Genome Center. "A lot of lives are going to be impacted because commercial companies are getting patents on these gene products, generating diagnostic tests, and making them widely available."

The ethical considerations of genetics begin with the research itself. There are some who argue, for instance, that researchers should not be in the business of mucking around with genes at all. But, says Dr. Claudio D. Stern, professor and chairman of genetics and development, "If so-called tinkering is not a desirable thing, then none of technology and medicine is desirable." Following that line of reasoning, he says, means that we should not develop new treatments for any illness at all, even one as common as heart disease; instead, people with heart disease should simply be allowed to die.

Much of the current concern over genetics stems from the public's misunderstanding of the goals of gene therapy, says Dr. Arthur Bank, professor of genetics and development and of medicine. But any cancer therapy has a risk of a certain amount of DNA breaking and mutating in cells. The potential complications associated with gene therapy are no greater than the risks inherent in chemotherapy, says Dr. Bank.

Likewise, notes Dr. Edelman, public fears that gene therapy will revive eugenics with projects aimed at building a "super race" are unfounded. "There isn't research being done on trying to do gene transfer experiments to ensure that your son is at least 6 feet tall or your daughter has blue eyes. No one is even close to saying that if we manipulate these genes, your daughter will be a mathematical genius and your son will outdo Jascha Heifetz on the violin."

Dr. Arthur Bank

Fears about eugenics and tinkering are unfounded, but ethical dilemmas over testing abound. Once a test becomes available for a genetically linked disorder, the question arises of who should be tested. With diseases for which a treatment or preventative measure is available, testing is generally-but not always-seen as beneficial. For other conditions, however, the benefits of genetic screening are less clear cut.

For instance, now that researchers have located genes connected with breast cancer-BRCA1 and BRCA2-tests to screen women for these defects will soon be commonplace. But, says Dr. Bank, a nationwide genetic screening program for the disease would raise several ethical issues. "About 90 percent of people who develop sporadic breast cancer will not have the BRCA1 gene. So you can't tell people who test negative that they are not at risk for breast cancer," he says. "On the other hand, you can have false positives. It's tricky." Until more is known about all the genetic and environmental factors that lead to the development of a disease, broad recommendations for genetic screening cannot be made.

Conditions such as Huntington's disease, which is caused by a single gene, present an even more complicated picture. The decision of whether to test can be an intensely personal one because no treatment is available for this fatal disease. "Do you want to know how and when you are going to die, especially if you have no power to change the outcome?" asks Dr. Nancy Wexler, the Higgins Professor of Neuropsychology and a leader in the successful search for the gene that causes Huntington's. "How does a person choose to learn this momentous information? How does one cope with the answer?"
In answer to such questions, some would say that genetic testing should be limited to diseases for which a treatment exists. Others disagree.

Limiting testing to treatable diseases is short-sighted, says Dr. Edelman. "Some people want to know, so they can know how to pattern their lives. If I knew I was going to have Huntington's disease and was going to die of this terrible neurological disorder in my late 40s or 50s, I might decide not to marry, for instance. I wouldn't want to have to agonize over the consequences to my wife and children of my dying at age 50." Other people in the same circumstances might choose differently.

This situation also poses a difficult problem for physicians, who may be placed in the position of advising patients whether to undergo testing. "Under what circumstances should physicians urge patients to secure tests about possible conditions that are late-onset?" asks Harold Edgar, the Julius Silver Professor of Law, Science, and Technology at Columbia's School of Law.

Dr. Nancy Wexler

In fact, says Dr. Wexler, the culture of genetic counseling-which is emphatically non-directive-is most likely headed for a clash with traditional medicine, which has a history of being directive. "The job of a genetic counselor is not to urge someone to take a test, but to provide information and counseling with which they can make a decision. This is especially important since a lot of decisions about testing affect child-bearing and reproductive issues," she says. "But when you're trying to create genetic services, how do you get the two cultures of medicine and genetic counseling to co-exist?"

Furthermore, with genetic diseases, the decision to test or not can go beyond the individual. For instance, when one individual is tested for Huntington's disease, the genetic risk for the entire family can be implicated: If a parent tests positive for the gene, his or her offspring have a 50 percent risk of also being affected. "This has an enormous impact," says Dr. Wexler. "These are family diseases."

As director of the genetics diagnostic laboratory for Presbyterian Hospital, Dr. Dorothy Warburton, professor of clinical genetics and development, has encountered situations where individuals are found to be carrying chromosome rearrangements that could result in children with birth defects. Yet these individuals often don't want to let their siblings know the results because the knowledge could put a stigma on their family in the community. "People often want to hide this type of information," says Dr. Warburton, "but their family may have a right to know. There's a conflict between our responsibility to the patient and our broader responsibility to the community." The genetic clinic's policy is to respect a patient's wishes but to discuss the consequences.

Although the technology exists to diagnose thousands of conditions, labs such as Dr. Warburton's routinely screen for only a few abnormalities. As more and more genetic links to various diseases are found, however, the public may demand that those tests be done-and at an earlier and earlier age. In many cases, the rationale behind prenatal testing will be to avoid the heartbreak of watching a child suffer with a devastating disease. But some experts worry that genetic testing will be put to other uses-that in the quest for a "perfect" baby, people may choose to terminate a pregnancy if any abnormality, no matter how insignificant, shows up on a genetic test. The meaning of "ethical" in these cases has not been defined.

"What if a prenatal test turns up a gene for Alzheimer's or breast cancer?" asks Professor Edgar. "Is it appropriate to have an abortion, when it can take 70 years for Alzheimer's to develop?" Milder conditions pose the same dilemma. Dr. Ruth Ottman, associate professor in the Gertrude H. Sergievsky Center and the School of Public Health, recently identified a genetic link for a form of partial epilepsy, in which most affected individuals have well-controlled seizures (though the disease does not always take this mild form). "It's hard to imagine a situation in which it would be appropriate to screen for this prenatally," she says. "It's not a life-threatening condition."

The increasing availability of genetic tests also may mean that individuals will face increasing pressures to be tested for a wide range of conditions before obtaining health insurance or jobs, for instance. If tests determine that at age 12 or 15 an individual is carrying a gene for cancer and at age 21 or 22 he or she wants to go to medical school, Dr. Edelman asks, can the medical school refuse enrollment on the grounds that the student won't have a long career? Can the armed forces do the same? How will health insurance companies handle this type of information? "If health insurance can eliminate people with diabetes as not being in a normal risk group, how about people with an 80 percent chance of developing cancer?" he says.

Dr. Wexler cites the case of one young woman who had to force her health insurance to pay for a prophylactic mastectomy after her BRCA1 test came up positive. Shortly after it was over, the woman was laid off. "Often, the aims of genetic testing and health insurance are contradictory, especially in the age of managed care," she says.

Dr. Ruth Ottman

In some cases, such discrimination may happen even if a test is inconclusive. Dr. Richard Mayeux, the Gertrude H. Sergievsky Professor of Neurology, Psychiatry, and Public Health and director of the Sergievsky Center, recently confirmed a link between an increased risk of Alzheimer's disease and the apolipoprotein-E gene (APO-E). "The presence of the apolipoprotein-E gene indicates there is a genetic risk factor for Alzheimer's disease, but it does not guarantee that the disease will develop," says Dr. Mayeux. In an article in the September issue of the American Journal of Public Health, Dr. Mayeux and his colleague Dr. Nicole Schupf expressed concern that a new commercial test to detect the APO-E gene might be misused. "The temptation may exist for employers or insurers to use the APO-E test to avoid hiring or insuring people who have the gene, even though they may never develop the disease," says Dr. Mayeux. He and Dr. Schupf recommend that APO-E genotypes not be made available to third parties such as insurers or employers until genotypic risks are fully understood.

Other experts worry that information gained from genetic tests will find its way into the realm of personal relationships. Frank P. Grad, the J.P. Chamberlain Professor Emeritus of Legislation and former director of the Legislative Drafting Research Fund, foresees the day when a genetic bill of health might be a consideration for entering into a relationship or marriage when having children is a possibility. Currently, the law says a person who is HIV-positive is obligated to tell that information to another person before having sex with him or her. Consenting to sexual relations is not the same as consenting to contracting a fatal disease, notes Professor Grad, who was principal investigator on "Lawful Uses of Knowledge from the Human Genome Project," a report prepared under a U.S. Department of Energy Ethical, Legal, and Social Issues grant. It's possible this same principle could be applied to genetics. "If people produce children, it's not a situation in which someone 'infects' another person. But if the child then inherits a genetic disease, that seems to me to be as devastating as giving someone an incurable transmissible disease."

Society's need to know will impact directly on an individual's right to keep genetic information private. That privacy right becomes highly questionable when others are involved, says Professor Grad. Indeed, even the right not to be tested ought not to be protected if it's used as a shield for not informing others, he says.

"People want to make genetic information part of their deepest, darkest privacy concerns-but we don't protect privacy anyway," he says. "There is no law anywhere that provides across-the-board privacy for genetic information. Privacy is much more honored in theory than in reality, and that theory is then used as a device to avoid certain public health initiatives." As we continue to discover and utilize new genetic links to diseases, the challenge will be to balance privacy with the need for public health protection. Says Professor Grad, "I believe it can be done if we devote more time and attention to public education on genetics and its public health ramifications."

Devoting more time to genetics research would help ease some of the ethical issues by providing new treatment options, says Dr. Wexler. "The real aim of research-the whole push for researchers and for the families involved-is treatment or a cure," she says. "Then there would be more of a reason to get tested."

In the meantime, however, most experts agree it will be a long time before society catches up with science. "There are so many complications and subtleties to these issues that I don't know of any set of principles or even proposed legislation that will solve all the problems," says Dr. Edelman. "But this issue is just exploding. We are going to have to sort through these questions and start doing things that will lead to a policy decision or legislation. And we're going to have to do it soon."